Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies.

Abstract

OBJECTIVE:

Preeclampsia is a syndrome characterized by hypertension and poor placental development. The developmental wingless (Wnt) pathway plays an important role in placental development and we hypothesized that Wnt signaling would be dysregulated in preeclampsia.

METHODS:

To elucidate aberrations in the Wnt signaling pathway we conducted a pathway analysis on placental mRNA in late-onset preeclampsia and normal pregnancy from the STORK study [n = 10 in each group, RNA sequencing (RNAseq)] to identify differentially expressed genes. In addition, we compared circulating levels of secreted Wnt agonists and antagonists at term pregnancy and 6 months postpartum from an acute preeclampsia study (preeclampsia n = 34, normal pregnancy n = 61).

RESULTS:

We found circulating and placental mRNA levels of the secreted Wnt agonist R-spondin 3 (RSPO3) at term elevated in preeclampsia. Increased plasma RSPO3 was associated with high mean arterial pressure. Further, pathway analysis of placental tissue revealed elevated mRNA levels of upstream ligands WNT6 and WNT10A and frizzled receptors 2 and 4 in preeclampsia and downstream activation of the noncanonical Ca/NFAT pathway. Finally, plasma dickkopf 3 was decreased in preeclampsia 6 months postpartum.

CONCLUSION:

We identify a potential role for RSPO3 and activation of noncanonical Wnt signaling in preeclampsia.

• Authors: Thor Ueland, Mette-Elise Estensen, Guro Grindheim, Jens Bollerslev, Tore Henriksen, Pål Aukrust, Svend Aakhus, Lars Gullestad, Tove Lekva
• Journal: Journal of hypertension (J Hypertens) Vol. 38 Issue 7 Pg. 1347-1354 (07 2020) ISSN: 1473-5598 [Electronic] England
• PMID: 31990902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• RNA, Messenger
• RSPO3 protein, human
• Thrombospondins
• WNT10A protein, human
• WNT6 protein, human
• Wnt Proteins

Topics

• Adult
• Base Sequence
• Biopsy
• Female
• Gene Expression Regulation
• Humans
• Hypertension (metabolism)
• Ligands
• Placenta (metabolism)
• Postpartum Period
• Pre-Eclampsia (metabolism)
• Pregnancy
• Pregnancy Trimester, Third
• RNA, Messenger (genetics)
• Signal Transduction
• Thrombospondins (genetics)
• Wnt Proteins (genetics)